Ethnic differences in clinical pain have been observed across numerous acute and chronic conditions, with African Americans often reporting higher levels of pain and disability. While multiple factors inevitably determine these ethnic differences, we have proposed that ethnic differences in endogenous pain modulation may represent an important contributor. During the previous funding cycle, we have gathered substantial evidence documenting differences in experimental pain sensitivity and endogenous pain modulation in a population of healthy African Americans, Hispanic Americans, and non-Hispanic whites. Relative to non- Hispanic whites, both minority groups evinced significantly greater sensitivity to suprathreshold heat, cold, and ischemic stimuli. Moreover, compared to non-Hispanic whites, African Americans showed reduced diffuse noxious inhibitory controls (DNIC), suggesting diminished pain inhibitory capacity. In this competing renewal application, we propose to translate our findings to a clinical population by addressing the following specific aims: 1) to characterize ethnic differences in experimental pain sensitivity, endogenous pain inhibition, clinical pain and pain-related disability among older African Americans and non-Hispanic whites with knee osteoarthritis (OA). In order to accomplish this aim, we will obtain psychophysical measures of pain perception and pain inhibition (i.e. diffuse noxious inhibitory controls, DNIC) as well as measures of clinical pain and disability; 2) to determine ethnic group differences in biological, psychological, and sociocultural factors and their contribution to pain sensitivity, pain inhibition, and clinical pain and disability among older African Americans and non-Hispanic whites with knee OA; and 3) to determine whether the combination of laboratory measures of pain sensitivity and pain inhibition along with biological, psychological and sociocultural factors mediate ethnic group differences in clinical pain and pain-related disability among older African Americans and non-Hispanic whites with knee OA. We anticipate that, relative to non-Hispanic whites, African Americans will report higher levels of OA-related pain and disability, and these differences in clinical pain and disability will be mediated by ethnic group differences in laboratory measures of pain sensitivity and pain inhibition, in combination with biological and psychosocial variables. Support for our hypotheses will provide novel information regarding the clinical utility of laboratory measures of endogenous pain modulation for explaining ethnic group differences in OA-related pain and disability. PUBLIC HEALTH RELEVANCE: Project Narrative Ethnic differences in clinical pain and pain-related disability have been well documented, and ethnic differences in experimental pain sensitivity have been reported among healthy adults. The goal of this project is to determine whether ethnic differences in laboratory measures of pain sensitivity and pain inhibition, in combination with biological and psychosocial variables, mediate ethnic group differences in clinical pain and disability among African Americans and non-Hispanic whites with knee osteoarthritis.